Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo
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Cuixia Yang1,2,*, Yiqing He1,*, Huizhen Zhang3, Yiwen Liu1, Wenjuan Wang2, Yan Du1 and Feng Gao1,2
1 Department of Molecular Biology Laboratory, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China
2 Department of Clinical Laboratory, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China
3 Department of Pathology, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China
* These authors are co-first authors
Feng Gao, email:
Keywords: CD44, breast cancer, selective targeting therapy, hyaluronan
Received: October 20, 2014 Accepted: March 06, 2014 Published: March 29, 2015
The cell surface glycoprotein CD44 is expressed in cancer cells and has been used as a therapeutic target in preclinical studies. However, the ubiquitous expression of CD44 in numerous cell types, including hematopoietic cells, has hindered its application in targeted therapy. Here, we demonstrated that CD44 was activated on breast cancer cells but was inactive on normal cells in vitro and in vivo. We analyzed 34 clinical primary tumor and normal breast tissues and demonstrated that CD44 was in an active state on breast cancer cells but in an inactive state on normal cells. Furthermore, based on the binding property of CD44 with its ligand hyaluronan (HA), we self-assembled HA-coated nanoparticles and studied their selective targeting efficacy. Our results indicate that HA-coated nanoparticles bearing the CD44 ligand selectively targeted cancer cells both in vitro and in vivo, killing breast cancer cells while sparing normal cells. Our study suggested that the active state of CD44 plays a crucial role in the selective targeting of breast cancer cells by avoiding nonspecific toxicity to CD44-quiescent normal cells. These findings may provide a new idea for the selective targeting of cancer cells in other human cancers.
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